Special K: Is Ketamine Really All That?

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Clinical use first reported in human medicine in 1965; approved for clinical use in 1970First identified veterinary report: Glen JB. The use of ketamine (CI-581) in feline anaesthetic practice. Vet Rec 1973.

Unravelling story with respect to evidence-based medicine – in people and especially veterinary species. Less so regarding use in anaesthesia, more so regarding sedation and especially analgesia.

“Ketamine may be the subject of misuse and, therefore, should be stored in the controlled drugs cabinet and its use recorded in an informal register.” (RCVS website, March 2015)

1. How does ketamine work? What does it do?

N-methyl-D-aspartate (NMDA) receptor antagonist:

Most widely reported and acknowledged mechanism; thought to be responsible for most clinical effects

But “nightmare of the pharmacologist” as myriad other proven/suggested mechanisms and receptors may be involved

Overlap between dose ranges for clinical effects; also depends on individual patient.

Analgesia:

Low/sub-dissociative dose use for analgesia has gained increasing recognition and popularity in last 10 years or soAnalgesic uses include acute emergency pain but also perioperative pain managementTypically as infusion after initial loading dose for analgesia but intermittent bolus therapy also feasibleAnalgesic effects both supra-spinal (brain) and spinalLikely to have both more classically reported anti-sensitisation (“wind up”) CNS effects and direct analgesia

3. Is ketamine contraindicated with raised intracranial pressure?

Long-standing contraindication in veterinary references – seems to have been extrapolated from human references.Long-standing contraindication in human references – based on small number of poor quality studies from 1970s.

Active on-going clinical research in humans with raised ICP of different causes (e.g. trauma vs. mass lesion vs. hydrocephalus) to test traditional contraindicationIncreasing consensus at this time refuting this contraindication and supporting positive risk-benefit profile for ketamine use in general population of acute emergency human patients with suspected/proven raised ICP

Original contraindication reported in veterinary resources extrapolated from human medicine with no species-specific evidence. At this time it seems reasonable and legitimate to discard this ‘myth’ while keeping future evidence under review.

5. What about ketamine in cats with hypertrophic cardiomyopathy (HCM)?

Meant to be relatively contraindicated in cats with HCM; sympathomimetic effect may cause a cat with sub-clinical cardiomyopathy to decompensate – especially if obstructive component to HCM.Relative not absolute contraindication – risk-benefit profile as alwaysUndoubtedly many cats with sub-clinical HCM will have received ketamine and true significance/risk remains unclear

7. Can ketamine be used as a sole agent?

Is it okay for a patient not to have already received another agent (e.g. opioid) that is on board and working at the time of ketamine administration? Or indeed not to at least have one with a rapid onset co-administered alongside the ketamine?

Sole use of ketamine reported in children and seems more recognisedEvidence in adult humans does not seem to support sole useSuggest (anecdotally) never using ketamine as sole agent in veterinary species – especially due to increased risk of potentially spectacular “ketamine head”

8. Is ketamine contraindicated with raised intraocular pressure?

Another long-standing listed contraindication in human and veterinary medicine; again substantive evidence woefully lackingIncreasingly rebutted as a ‘myth’ in human medicine based on emerging evidenceNo good quality clinically relevant canine/feline evidence identifiedAuthor is comfortable to recommend use of ketamine in patients with raised IOP where potential benefits supersede this theoretical and unproven risk

9. Ketamine in caesarean section:

Can and indeed should you be including ketamine as part of your c-section protocol?Used in women relatively commonly for this purpose; no evidence identified that poses increased risk to mum or babyPaucity of veterinary evidence and certainly identified demonstrating increased risk“Absence of evidence is not evidence of absence” but overall happy to recommend pre-, intra- and post-operative ketamine use for c-sectionProvides multimodal analgesia. Dose-sparing for potentially more harmful drugs, especially inhalant anaesthetics

10. Other bits ‘n’ pieces:

Other things to highlight about ketamine:Protective airway reflexes preserved

Cats’ eyes remain open – must keep well lubricated

Cats reportedly may salivate excessively – reported more in humans

Hepatic metabolism in most species; minimal in cats

Parent compound and metabolites renally excreted. Available evidence in people at this time does not suggest the need for dose reduction with hepatic or renal impairment.

Use in treatment of refractory status epilepticus reported in people; one published canine case report but actual unpublished clinical experience likely to be greater than this.

Also sometimes used in children with refractory status asthmaticus due to potential bronchodilatory effect from β2-adrenergic receptor stimulation. Unclear if effective in asthmatic cats refractory to standard therapies – very rare patient anyway?

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